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1.
bioRxiv ; 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38076874

ABSTRACT

Many cytoskeletal networks consist of individual filaments that are organized into elaborate higher order structures. While it is appreciated that the size and architecture of these networks are critical for their biological functions, much of the work investigating control over their assembly has focused on mechanisms that regulate the turnover of individual filaments through size-dependent feedback. Here, we propose a very different, feedback-independent mechanism to explain how yeast cells control the length of their actin cables. Our findings, supported by quantitative cell imaging and mathematical modeling, indicate that actin cable length control is an emergent property that arises from the cross-linked and bundled organization of the filaments within the cable. Using this model, we further dissect the mechanisms that allow cables to grow longer in larger cells, and propose that cell length-dependent tuning of formin activity allows cells to scale cable length with cell length. This mechanism is a significant departure from prior models of cytoskeletal filament length control and presents a new paradigm to consider how cells control the size, shape, and dynamics of higher order cytoskeletal structures.

2.
Nanotechnology ; 34(28)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37040718

ABSTRACT

Transition metal dichalcogenide (TMDC) monolayers with their direct band gap in the visible to near-infrared spectral range have emerged over the past years as highly promising semiconducting materials for optoelectronic applications. Progress in scalable fabrication methods for TMDCs like metal-organic chemical vapor deposition (MOCVD) and the ambition to exploit specific material properties, such as mechanical flexibility or high transparency, highlight the importance of suitable device concepts and processing techniques. In this work, we make use of the high transparency of TMDC monolayers to fabricate transparent light-emitting devices (LEDs). MOCVD-grown WS2is embedded as the active material in a scalable vertical device architecture and combined with a silver nanowire (AgNW) network as a transparent top electrode. The AgNW network was deposited onto the device by a spin-coating process, providing contacts with a sheet resistance below 10 Ω sq-1and a transmittance of nearly 80%. As an electron transport layer we employed a continuous 40 nm thick zinc oxide (ZnO) layer, which was grown by atmospheric pressure spatial atomic layer deposition (AP-SALD), a precise tool for scalable deposition of oxides with defined thickness. With this, LEDs with an average transmittance over 60% in the visible spectral range, emissive areas of several mm2and a turn-on voltage of around 3 V are obtained.

3.
Pharmaceutics ; 14(8)2022 Aug 09.
Article in English | MEDLINE | ID: mdl-36015281

ABSTRACT

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.

4.
Front Oncol ; 12: 812777, 2022.
Article in English | MEDLINE | ID: mdl-35875083

ABSTRACT

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r2 = 0.32; women, r2 = 0.22), and thus SUV and SULCT were also weakly correlated (men, r2 = 0.24; women, r2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials.

5.
Healthc (Amst) ; 9(2): 100508, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33711564

ABSTRACT

Research and media reports about coronavirus disease 2019 (COVID-19) have largely focused on urban areas due to their high caseloads. However, the COVID-19 pandemic presents distinct and under-recognized challenges to rural areas. This report describes the challenges faced by Bassett Healthcare Network (BHN), a health network in rural upstate New York, and the strategies BHN devised in response. The response to COVID-19 at BHN focused on 4 strategies: (1) Expansion of intensive-care capacity. (2) Redeployment and retraining of workforce. (3) Provision of COVID-19 information, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and appropriate follow-up for a geographically dispersed population. (4) Coordination of the response to the pandemic across a large, diverse organization. Rural health systems and hospitals can take steps to address the specific challenges posed by the COVID-19 pandemic in their communities. We believe that the strategies BHN employed to adapt to COVID-19 may be useful to other rural health systems. More research is needed to determine which strategies have been most effective in responding to the pandemic in other rural settings.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/organization & administration , Hospitals, Rural/organization & administration , Rural Health , Hospital Planning , Humans , New York/epidemiology , Pandemics , SARS-CoV-2 , Telemedicine
6.
Am J Infect Control ; 49(6): 818-824, 2021 06.
Article in English | MEDLINE | ID: mdl-33253763

ABSTRACT

OBJECTIVE: Identify research gaps relevant to the global effort to combat antimicrobial resistance. METHODS: Web of Science, PubMed, Scopus, and Ovid MEDLINE were searched for reviews on antimicrobial resistance published between January 1, 2015 and December 31, 2019. Recommendations for future research were identified. FINDINGS: Seventy-four reviews met inclusion criteria; 300 research gaps and recommendations were identified. The largest number were from the human health sector (105; 35%) followed by environmental health (72; 23%), animal health (66; 22%), food and feed (14; 5%), and plants and crops (8; 3%); 35 (12%) involved more than one sector. The largest number of gaps concerned surveillance of resistance (68; 23%), followed by study design or methodology (52; 17%), interventions (41; 14%), risk assessment and modeling (35; 12%), ecological (26; 9%) and biochemical (28; 9%) aspects of resistance, interface between reservoirs of resistant pathogens (24; 8%), and economic (15; 5%) and awareness- and behavior-related (11; 4%) aspects of antimicrobial resistance. CONCLUSIONS: Important research gaps remain in our complete understanding of antimicrobial resistance, and more research is needed about its development, transmission, and impact across the interface of human, animal, and environmental reservoirs.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Animals , Anti-Bacterial Agents/pharmacology , Humans , Research Design , Risk Assessment
7.
Clin Infect Dis ; 73(7): e1927-e1935, 2021 10 05.
Article in English | MEDLINE | ID: mdl-32730625

ABSTRACT

BACKGROUND: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. METHODS: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). RESULTS: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). CONCLUSIONS: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Adolescent , Adult , CD4 Lymphocyte Count , Cost-Benefit Analysis , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Quality-Adjusted Life Years , United States/epidemiology , Young Adult
9.
BMJ Open ; 10(5): e032579, 2020 05 12.
Article in English | MEDLINE | ID: mdl-32404384

ABSTRACT

BACKGROUND AND OBJECTIVE: Simulation models can project effects of tobacco use and cessation and inform tobacco control policies. Most existing tobacco models do not explicitly include relapse, a key component of the natural history of tobacco use. Our objective was to develop, calibrate and validate a novel individual-level microsimulation model that would explicitly include smoking relapse and project cigarette smoking behaviours and associated mortality risks. METHODS: We developed the Simulation of Tobacco and Nicotine Outcomes and Policy (STOP) model, in which individuals transition monthly between tobacco use states (current/former/never) depending on rates of initiation, cessation and relapse. Simulated individuals face tobacco use-stratified mortality risks. For US women and men, we conducted cross-validation with a Cancer Intervention and Surveillance Modeling Network (CISNET) model. We then incorporated smoking relapse and calibrated cessation rates to reflect the difference between a transient quit attempt and sustained abstinence. We performed external validation with the National Health Interview Survey (NHIS) and the linked National Death Index. Comparisons were based on root-mean-square error (RMSE). RESULTS: In cross-validation, STOP-generated projections of current/former/never smoking prevalence fit CISNET-projected data well (coefficient of variation (CV)-RMSE≤15%). After incorporating smoking relapse, multiplying the CISNET-reported cessation rates for women/men by 7.75/7.25, to reflect the ratio of quit attempts to sustained abstinence, resulted in the best approximation to CISNET-reported smoking prevalence (CV-RMSE 2%/3%). In external validation using these new multipliers, STOP-generated cumulative mortality curves for 20-year-old current smokers and never smokers each had CV-RMSE ≤1% compared with NHIS. In simulating those surveyed by NHIS in 1997, the STOP-projected prevalence of current/former/never smokers annually (1998-2009) was similar to that reported by NHIS (CV-RMSE 12%). CONCLUSIONS: The STOP model, with relapse included, performed well when validated to US smoking prevalence and mortality. STOP provides a flexible framework for policy-relevant analysis of tobacco and nicotine product use.


Subject(s)
Cigarette Smoking/psychology , Computer Simulation/statistics & numerical data , Smoking Cessation/methods , Tobacco Use/psychology , Adult , Aged , Aged, 80 and over , Calibration , Cigarette Smoking/mortality , Female , Humans , Male , Middle Aged , Nicotine/adverse effects , Outcome Assessment, Health Care , Prevalence , Recurrence , Research Design , Smoking/epidemiology , Smoking/trends , Smoking Cessation/statistics & numerical data , United States/epidemiology
10.
Clin Exp Dermatol ; 45(3): 333-336, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31587342

ABSTRACT

Staphylococcal scalded skin syndrome (SSSS) is a disease caused by certain toxigenic strains of Staphylococcus aureus. While the classic severe phenotype is widely recognized in children, SSSS in fact exists on a spectrum with mild and moderate variants. Misunderstanding the phenotypic spectrum of SSSS may result in misdiagnosis of an otherwise treatable condition. To increase awareness of the heterogeneity of SSSS, we report four cases that together represent a range of clinical presentations.


Subject(s)
Skin/pathology , Staphylococcal Scalded Skin Syndrome/diagnosis , Staphylococcal Scalded Skin Syndrome/pathology , Child , Female , Humans , Infant , Male , Patient Acuity , Phenotype , Staphylococcal Scalded Skin Syndrome/classification
11.
Case Rep Oncol ; 12(3): 791-795, 2019.
Article in English | MEDLINE | ID: mdl-31762750

ABSTRACT

Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.

12.
Clin Nucl Med ; 44(9): 719-727, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31205149

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the efficacy of Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. METHODS: MEDLINE, EMBASE, and Ovid were systematically searched with keywords "lutetium," "Lu-177," "PRRT," "neuroendocrine," and "prognosis." Studies evaluating treatment with Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models. RESULTS: Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%-38.9%), and disease control rate was 74.1% (95% CI, 67.8%-80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%-41.5%), and disease control rate was 81.1% (95% CI, 76.4%-85.4%). CONCLUSIONS: Induction therapy, typically 4 treatments, with Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates.


Subject(s)
Lutetium/therapeutic use , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/radiotherapy , Radioisotopes/therapeutic use , Receptors, Peptide/metabolism , Humans , Neoadjuvant Therapy , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathology , Prognosis
13.
Pharmaceutics ; 10(1)2018 Feb 22.
Article in English | MEDLINE | ID: mdl-29470434

ABSTRACT

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers ran the 'Bruce' treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The 'Bruce' criterion heart rate is 85% of [220-age]. Approximately one minute before reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1-3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers rest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2ß of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2ß, CLTB and Vss values were comparable to those reported previously for rested volunteers. The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

14.
J Adolesc Health ; 62(1): 22-28, 2018 01.
Article in English | MEDLINE | ID: mdl-29273141

ABSTRACT

PURPOSE: To assess the optimal age at which a one-time HIV screen should begin for adolescents and young adults (AYA) in the U.S. without identified HIV risk factors, incorporating clinical impact, costs, and cost-effectiveness. METHODS: We simulated HIV-uninfected 12-year-olds in the U.S. without identified risk factors who faced age-specific risks of HIV infection (.6-71.3/100,000PY). We modeled a one-time screen ($36) at age 15, 18, 21, 25, or 30, each in addition to current U.S. screening practices (30% screened by age 24). Outcomes included retention in care, virologic suppression, life expectancy, lifetime costs, and incremental cost-effectiveness ratios in $/year-of-life saved (YLS) from the health-care system perspective. In sensitivity analyses, we varied HIV incidence, screening and linkage rates, and costs. RESULTS: All one-time screens detected a small proportion of lifetime infections (.1%-10.3%). Compared with current U.S. screening practices, a screen at age 25 led to the most favorable care continuum outcomes at age 25: proportion diagnosed (77% vs. 51%), linked to care (71% vs. 51%), retained in care (68% vs. 44%), and virologically suppressed (49% vs. 32%). Compared with the next most effective screen, a screen at age 25 provided the greatest clinical benefit, and was cost-effective ($96,000/YLS) by U.S. standards (<$100,000/YLS). CONCLUSIONS: For U.S. AYA without identified risk factors, a one-time routine HIV screen at age 25, after the peak of incidence, would optimize clinical outcomes and be cost-effective compared with current U.S. screening practices. Focusing screening on AYA ages 18 or younger is a less efficient use of a one-time screen among AYA than screening at a later age.


Subject(s)
Cost-Benefit Analysis , HIV Infections/epidemiology , Mass Screening/economics , Adolescent , Adult , Child , Female , Humans , Male , Quality-Adjusted Life Years , Risk Factors , United States , Young Adult
15.
Endocr Res ; 43(1): 11-14, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28742421

ABSTRACT

PURPOSE OF THE STUDY: To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients. MATERIALS AND METHODS: Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis. RESULTS AND CONCLUSIONS: Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.


Subject(s)
Ablation Techniques/adverse effects , Ablation Techniques/methods , Carcinoma, Papillary/radiotherapy , Iodine Radioisotopes/pharmacology , Outcome Assessment, Health Care , Sialadenitis/etiology , Thyroid Neoplasms/radiotherapy , Thyroiditis/etiology , Adult , Humans , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/adverse effects , Neoplasm Staging , Retrospective Studies , Thyroid Cancer, Papillary
16.
Clin Nucl Med ; 42(5): 350-353, 2017 May.
Article in English | MEDLINE | ID: mdl-28240668

ABSTRACT

Systemic radioisotope therapy with I-metaiodobenzylguanidine (I-MIBG) is an effective form of targeted therapy for neuroendocrine tumors. One of the absolute contraindications to administering I-MIBG therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of I-MIBG with no short-term adverse reactions.


Subject(s)
3-Iodobenzylguanidine/therapeutic use , Intestinal Neoplasms/radiotherapy , Neuroendocrine Tumors/radiotherapy , Radiopharmaceuticals/therapeutic use , Aged , Female , Humans , Intestinal Neoplasms/diagnostic imaging , Intestinal Neoplasms/pathology , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/secondary , Renal Dialysis
17.
J Nucl Med ; 58(5): 791-798, 2017 May.
Article in English | MEDLINE | ID: mdl-27738005

ABSTRACT

A single-site prospective open-label clinical study with cyclotron-produced sodium 99mTc-pertechnetate (99mTc-NaTcO4) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99mTc-NaTcO4 eluted from a generator. Methods:99mTc-NaTcO4 was produced from enriched 100Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99mTc-NaTcO4, whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99mTc-NaTcO4 showed organ and whole-body distributions identical to those of conventional 99mTc-NaTcO4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99mTc-NaTcO4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99mTc was equivalent to that with generator-eluted 99mTc and had no particular features allowing discrimination between the 99mTc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99mTc-NaTcO4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99mTc-NaTcO4 in routine clinical practice.


Subject(s)
Cyclotrons/instrumentation , Radiation Injuries/etiology , Sodium Pertechnetate Tc 99m/adverse effects , Sodium Pertechnetate Tc 99m/pharmacokinetics , Thyroid Diseases/diagnostic imaging , Thyroid Diseases/metabolism , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Humans , Isotope Labeling/instrumentation , Male , Metabolic Clearance Rate , Middle Aged , Organ Specificity , Radiation Injuries/diagnosis , Radiation Injuries/prevention & control , Radionuclide Generators , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Sodium Pertechnetate Tc 99m/chemical synthesis , Tissue Distribution
18.
Clin Nucl Med ; 41(1): 53-4, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26562579

ABSTRACT

A 70-year-old woman presented with frequent episodes of hypoglycemia. Imaging revealed a 6-cm pancreatic mass with several liver lesions. The pancreatic mass was resected and confirmed to be a well-differentiated insulinoma. Surgery improved but did not resolve her hypoglycemic episodes, and she was referred for peptide receptor radionuclide therapy with 177Lu-DOTATATE to treat her residual disease. A modified protocol with a continuous IV dextrose infusion was used, and the treatments were well tolerated. After 4 induction and 2 maintenance treatments, her hypoglycemic symptoms resolved completely and her disease stabilized. She has been progression free for 24 months.


Subject(s)
Insulinoma/radiotherapy , Neuroendocrine Tumors/radiotherapy , Octreotide/analogs & derivatives , Organometallic Compounds/therapeutic use , Pancreatic Neoplasms/radiotherapy , Receptors, Peptide/metabolism , Aged , Female , Humans , Insulinoma/pathology , Neoplasm Metastasis , Neuroendocrine Tumors/pathology , Octreotide/therapeutic use , Pancreatic Neoplasms/pathology
19.
Clin Nucl Med ; 41(4): 319-20, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26359561

ABSTRACT

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).


Subject(s)
Antimony/adverse effects , Breast Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Radiopharmaceuticals/adverse effects , Technetium Compounds/adverse effects , Antimony/administration & dosage , Artifacts , Female , Humans , Middle Aged , Radiopharmaceuticals/administration & dosage , Technetium Compounds/administration & dosage
20.
Clin Nucl Med ; 41(2): 144-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26359562

ABSTRACT

A 26-year-old woman with a 5-year history of metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome with SDHB mutation, who had failed multiple treatment regimens and had transfusion dependent pancytopenia, presented with progressive liver and bone metastases. She was unable to sleep due to painful skull metastases and had severe weakness in her extremities that limited her mobility and daily activities. She was treated with 2 doses of Ra-dichloride (Xofigo, Ra) and had a dramatic improvement in pain control, mobility, and overall quality of life for 8 weeks, before passing away from pulmonary hemorrhage.


Subject(s)
Bone Neoplasms/radiotherapy , Neoplastic Syndromes, Hereditary/radiotherapy , Paraganglioma/radiotherapy , Radiopharmaceuticals/therapeutic use , Radium/therapeutic use , Succinate Dehydrogenase/genetics , Adult , Alpha Particles/therapeutic use , Bone Neoplasms/secondary , Female , Humans , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology , Palliative Care , Paraganglioma/genetics , Paraganglioma/pathology , Radioisotopes/therapeutic use
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